Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1974 Nov;243(1):243–266. doi: 10.1113/jphysiol.1974.sp010752

Thallium and the sodium pump in human red cells

J D Cavieres, J C Ellory
PMCID: PMC1330699  PMID: 4449062

Abstract

1. Thallium (Tl) inhibits the ouabain-sensitive K influx in human red cells in high-Na medium. At 1 mM external K concentration [Ko], the ouabain-sensitive K influx decreases steadily with increasing Tl concentration, up to 0·9 mM outside; at 0·17 mM-Ko, however, Tl stimulates the ouabain-sensitive K influx below 0·1 mM-Tlo and inhibits it at higher concentrations.

2. In a K-free medium in which all except 5 mM-Na is replaced by choline, and into which red cells show zero control ouabain-sensitive Na efflux, Tl is able to support ouabain-sensitive Na efflux up to 2·1 m-mole/l. cells.hr following a sigmoid activation curve which is half-maximal between 0·03 and 0·05 mM-Tlo and that follows two-site kinetics up to 0·1 mM-Tlo. Beyond 0·15 mM-Tlo, the Tl-activated ouabain-sensitive Na efflux attained is inhibited slightly.

3. When the ouabain-sensitive Na efflux is measured at 5 mM-Nao and 5 mM-Ko, increasing concentrations of Tl have little effect on it, 0·9 mM-Tlo inhibiting by some 14%; in similar conditions, the ouabain-sensitive K influx is inhibited by about 40%.

4. The dependence of ouabain-sensitive K influx on external K concentration at 5 mM-Nao, which follows a slightly sigmoid curve in the absence of Tl, changes to hyperbolic at 0·06 mM-Tlo at the same time that ouabain-sensitive K influx is inhibited. The fitted Vmax values for ouabain-sensitive K influx are the same in the presence and in the absence of 0·06 mM-Tlo.

5. In high-Na cells, loaded by nystatin treatment, the ouabain-sensitive K influx measured at 0·2 mM-Nao follows a hyperbolic curve between 0·05 and 0·4 mM-Ko, and is inhibited by Tl in a strictly competitive fashion.

6. The effects of Tl on ouabain-sensitive Na efflux and ouabain-sensitive K influx are interpreted in terms of a high-affinity substitution for K at the external K sites of the Na pump and suggest that in human red cells Tl can be actively transported inwards in exchange for internal Na.

7. Thallium can inhibit about 25% of the ouabain-insensitive Na efflux into 5 mM-Nao and part of this inhibition occurs with a high Tl-affinity; the ouabain-insensitive K influx is inhibited by Tl both in high-Na and in 5 mM-Na medium, but with a different concentration dependence than the ouabain-insensitive Na efflux.

Full text

PDF
245

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brading A. F., Jones A. W. Distribution and kinetics of CoEDTA in smooth muscle, and its use as an extracellular marker. J Physiol. 1969 Feb;200(2):387–401. doi: 10.1113/jphysiol.1969.sp008700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Britten J. S., Blank M. Thallium activation of the (Na+--K+)-activated ATPase of rabbit kidney. Biochim Biophys Acta. 1968 Apr 24;159(1):160–166. doi: 10.1016/0005-2744(68)90254-4. [DOI] [PubMed] [Google Scholar]
  3. Cass A., Dalmark M. Equilibrium dialysis of ions in nystatin-treated red cells. Nat New Biol. 1973 Jul 11;244(132):47–49. doi: 10.1038/newbio244047a0. [DOI] [PubMed] [Google Scholar]
  4. Diamond J. M., Wright E. M. Biological membranes: the physical basis of ion and nonelectrolyte selectivity. Annu Rev Physiol. 1969;31:581–646. doi: 10.1146/annurev.ph.31.030169.003053. [DOI] [PubMed] [Google Scholar]
  5. Ellory J. C., Nibelle J., Smith M. W. The effect of salt adaptation on the permeability and cation selectivity of the goldfish intestinal epithelium. J Physiol. 1973 May;231(1):105–115. doi: 10.1113/jphysiol.1973.sp010222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. GEHRING P. J., HAMMOND P. B. THE UPTAKE OF THALLIUM BY RABBIT ERYTHROCYTES. J Pharmacol Exp Ther. 1964 Aug;145:215–221. [PubMed] [Google Scholar]
  7. Garay R. P., Garrahan P. J. The interaction of sodium and potassium with the sodium pump in red cells. J Physiol. 1973 Jun;231(2):297–325. doi: 10.1113/jphysiol.1973.sp010234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Garrahan P. J., Glynn I. M. Facftors affecting the relative magnitudes of the sodium:potassium and sodium:sodium exchanges catalysed by the sodium pump. J Physiol. 1967 Sep;192(1):189–216. doi: 10.1113/jphysiol.1967.sp008296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Garrahan P. J., Glynn I. M. The behaviour of the sodium pump in red cells in the absence of external potassium. J Physiol. 1967 Sep;192(1):159–174. doi: 10.1113/jphysiol.1967.sp008294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Garrahan P. J., Glynn I. M. The sensitivity of the sodium pump to external sodium. J Physiol. 1967 Sep;192(1):175–188. doi: 10.1113/jphysiol.1967.sp008295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Glynn I. M., Lew V. L., Lüthi U. Reversal of the potassium entry mechanism in red cells, with and without reversal of the entire pump cycle. J Physiol. 1970 Apr;207(2):371–391. doi: 10.1113/jphysiol.1970.sp009067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hille B. Potassium channels in myelinated nerve. Selective permeability to small cations. J Gen Physiol. 1973 Jun;61(6):669–686. doi: 10.1085/jgp.61.6.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hille B. The permeability of the sodium channel to metal cations in myelinated nerve. J Gen Physiol. 1972 Jun;59(6):637–658. doi: 10.1085/jgp.59.6.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hoffman J. F., Kregenow F. M. The characterization of new energy dependent cation transport processes in red blood cells. Ann N Y Acad Sci. 1966 Jul 14;137(2):566–576. doi: 10.1111/j.1749-6632.1966.tb50182.x. [DOI] [PubMed] [Google Scholar]
  15. Hoffman P. G., Tosteson D. C. Active sodium and potassium transport in high potassium and low potassium sheep red cells. J Gen Physiol. 1971 Oct;58(4):438–466. doi: 10.1085/jgp.58.4.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Inturrisi C. E. Thallium activation of K+-activated phosphatases from beef brain. Biochim Biophys Acta. 1969 Apr;173(3):567–569. doi: 10.1016/0005-2736(69)90022-4. [DOI] [PubMed] [Google Scholar]
  17. Kayne F. J. Thallium (I) activation of pyruvate kinase. Arch Biochem Biophys. 1971 Mar;143(1):232–239. doi: 10.1016/0003-9861(71)90204-9. [DOI] [PubMed] [Google Scholar]
  18. Lew V. L., Hardy M. A., Jr, Ellory J. C. The uncoupled extrusion of Na+ through the Na+ pump. Biochim Biophys Acta. 1973 Oct 11;323(2):251–266. doi: 10.1016/0005-2736(73)90149-1. [DOI] [PubMed] [Google Scholar]
  19. POST R. L., MERRITT C. R., KINSOLVING C. R., ALBRIGHT C. D. Membrane adenosine triphosphatase as a participant in the active transport of sodium and potassium in the human erythrocyte. J Biol Chem. 1960 Jun;235:1796–1802. [PubMed] [Google Scholar]
  20. Post R. L., Hegyvary C., Kume S. Activation by adenosine triphosphate in the phosphorylation kinetics of sodium and potassium ion transport adenosine triphosphatase. J Biol Chem. 1972 Oct 25;247(20):6530–6540. [PubMed] [Google Scholar]
  21. Sachs J. R. Competitive effects of some cations on active potassium transport in the human red blood cell. J Clin Invest. 1967 Sep;46(9):1433–1441. doi: 10.1172/JCI105635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sachs J. R. Ouabain-insensitive sodium movements in the human red blood cell. J Gen Physiol. 1971 Mar;57(3):259–282. doi: 10.1085/jgp.57.3.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sachs J. R. Sodium movements in the human red blood cell. J Gen Physiol. 1970 Sep;56(3):322–341. doi: 10.1085/jgp.56.3.322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sachs J. R., Welt L. G. The concentration dependence of active potassium transport in the human red blood cell. J Clin Invest. 1967 Jan;46(1):65–76. doi: 10.1172/JCI105512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Skulskii I. A., Manninen V., Järnefelt J. Interaction of thallous ions with the cation transport mechanism in erythrocytes. Biochim Biophys Acta. 1973 Mar 29;298(3):702–709. doi: 10.1016/0005-2736(73)90086-2. [DOI] [PubMed] [Google Scholar]
  26. WILKINSON G. N. Statistical estimations in enzyme kinetics. Biochem J. 1961 Aug;80:324–332. doi: 10.1042/bj0800324. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES